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Minocycline delays death of retinal ganglion cells in experimental glaucoma and after optic nerve transection.

Levkovitch-Verbin H, Kalev-Landoy M, Habot-Wilner Z, Melamed S

Sam Rothberg Ophthalmic Molecular Biology Laboratory, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel. halevko@hotmail.com

OBJECTIVE: To evaluate the effect of minocycline hydrochloride on the survival of retinal ganglion cells (RGCs) in glaucomatous rat eyes and rat eyes after optic nerve transection (ONT). METHODS: The effect of intraperitoneal injections of minocycline at dosages of 15 mg/kg per day, 22 mg/kg per day, and 45 mg/kg per day was evaluated and compared with saline in ONT (n = 174) and experimental glaucoma (n = 51). RESULTS: The mean +/- SEM survival rate of RGCs 1 week after ONT was significantly higher with minocycline at dosages of 15 mg/kg per day (36% +/- 3%; n = 9; P = .04), 22 mg/kg per day (44% +/- 2%; n = 15; P = .001), and 45 mg/kg per day (39% +/- 3%; n = 10; P = .008) compared with saline (29% +/- 2%; n = 28). Minocycline at a dosage of 22 mg/kg per day was also significantly neuroprotective compared with saline 2 weeks after ONT (mean +/- SEM survival rate, 5% +/- 1% vs 3% +/- 0.4%, respectively; n = 20 [10 rats in each group]; P = .03). In experimental glaucoma, the mean +/- SEM percentage of RGCs after 4 weeks was 84% +/- 4% in the minocycline group (n = 15) compared with 65% +/- 4% in the saline group (n = 18) (P = .003). Apoptosis of RGCs was significantly delayed by minocycline 4 days and 1 week after ONT. CONCLUSION: Minocycline significantly enhances the survival of RGCs after ONT and in experimental glaucoma by delaying the apoptosis pathway. CLINICAL RELEVANCE: The safety record of minocycline and its ability to penetrate the blood-brain barrier suggest that this drug is a promising neuroprotective drug for optic nerve injuries.

Published 11 April 2006 in Arch Ophthalmol, 124(4): 520-6.
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